DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Request for Reconsideration
Applicant's reply filed 4/13/2026 has been entered. The claims were not amended. Claims 37-49 and 56 remain pending, of which claims 44-49 and 56 are being considered on their merits. Claims 37-43 remain withdrawn from consideration. References not included with this Office action can be found in a prior action. Any rejections of record not particularly addressed below are withdrawn in light of the claim amendments and/or applicant’s comments.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 44-49 are rejected under 35 U.S.C. 103 as being unpatentable over Gagnon et al. (WO 2012/169970) in view of Mahn (2012; Hydrophobic interaction chromatography: fundamentals and applications in biomedical engineering. Rijeka, Croatia: INTECH Open Access Publisher).
Gagnon teaches a method of purifying exosomes (e.g. extracellular vesicles) secreted by mesenchymal stem cells, the method comprising equilibrate a hydroxyl monolith with a composition comprising 6% PEG 600 and 200 mM NaCl (e.g. controlling the hydrophobicity), loading the exosomes in a composition comprising PEG 6000 and NaCl, and eluting/recovering the exosomes (Example 22), reading in-part on steps (b)-(d) of claim 44, the embodiment of chloride as a salting out ion for claims 45-47. Gagnon envisions obtaining exosomes by hydrophobic interaction chromatography retaining sufficient polar character as an alternative to convective chromatography comprising a monolith material ([0105], [0120], [0133]-[0134], [0192]-[0193]), reading in-part on claim 44. Gagnon teaches obtaining exosomes from human stem cells (Example 30) and a cell culture harvest (claim 6), reading on the mammalian cell culture of claim 47. Gagnon further teaches Sephadex (e.g. Sepharose) (Example 26) and silica microspheres (e.g. beads, see Example 27), reading on those embodiments of claim 47. Gagnon teaches performing the isolation/recovery step prior to or after a method for fractionating the target species (e.g. exosomes from other materials and selected from the group consisting in-part of centrifugation and ultracentrifugation (claim 69), reading on claim 49.
Regarding claim 44, Gagnon does not teach a hydrophobic functional group lacking any polar functional groups. Regarding claim 48, Gagnon does not teach the embodiments of butyl, octyl, or phenyl functional groups/ligands.
Mahn teaches reviews the state of the art for hydrophobic interaction chromatography (Introduction on p603). Mahn teaches that in hydrophobic interaction chromatography, macromolecule retention occurs due to hydrophobic interactions between hydrophobic ligands immobilized on a stationary phases such as agarose or dextran or silica and hydrophobic moieties on the macromolecules, with butyl, octyl, and phenyl being the most commonly used ligands (subheading 202, on p604-605, Fig. 1 and 2), reading on claims 44 and 48.
Regarding claims 44 and 48, it would have been obvious to a person of ordinary skill in the art before the invention was filed to further substitute the hydrophobic interaction chromatography material having sufficient polar character of Gagnon with the hydrophobic interaction chromatography comprising butyl, octyl, or phenyl of Mahn. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because Mahn and Gagnon are directed in-part towards hydrophobic interaction chromatography and because Mahn teaches exemplary species of both stationary phase material and hydrophobic ligands The skilled artisan would have been motivated to do so because Gagnon does not teach any specific species of hydrophobic interaction chromatography material combined with exosomes, and so the substitution of the specific species of Mahn would predictably yield a hydrophobic interaction chromatography material comprising a known stationary phase with known hydrophobic ligands (e.g. butyl, octyl, and/or phenyl) in the exosome isolation methods of Gagnon. See M.P.E.P. § 2143 (B).
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Claim 56 is rejected under 35 U.S.C. 103 as being unpatentable over Gagnon and Mahn as applied to claim 44 above, and further in view of Raynes et al. (Analytical Biochemistry (1988), 173, 116-124) and Li et al. (Philos Trans R Soc Lond B Biol Sci (2014), 369(1652):20130502).
The teachings of Gagnon and Mahn are relied upon as set forth above.
Regarding claim 56, Gagnon and Mahn do not teach lipoprotein.
Raynes teaches methods comprising purification of high density apolipoproteins by hydrophobic interaction chromatography (HIC) from serum (Abstract; detailed methods on p117 at “hydrophobic interaction chromatography”).
Li teaches that exosomes are tiny vesicles (30–150 nm) constantly secreted by all healthy and abnormal cells, and found in abundance in all body fluids (Abstract). Li teaches the RNA within exosomes obtained from blood serum or urine would be advantageous source of biomarkers for cancer and neurodegenerative disorders (subheading “(d) Exosomes as a source of biomarkers”) on p6), reading on claim 56. Li teaches methods of obtaining exosomes from the blood or urine of subjects and then analyzing the RNA content by sequencing (1st paragraph under subhead 2 on p2, paragraph spanning both columns of p3, Fig. 2, and Table 1), reading on claim 56
It would have been obvious to a person of ordinary skill in the art before the invention was filed to substitute the exosomes obtained from stem cells of Gagnon with the blood serum comprising lipoproteins and exosomes and specific HIC methods of Raynes in view of Li. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because Raynes teaches detailed methods of HIC to separate lipoprotein(s) from blood serum, because Raynes and Gagnon are both directed towards HIC methods, because Li and Gagnon are directed towards exosomes and obtaining exosomes, and because Li teaches that blood serum inherently comprises exosomes. The skilled artisan would have been motivated to do so because Li teaches the RNA within exosomes obtained from blood serum or urine would be advantageous source of biomarkers for cancer and neurodegenerative disorder, and so Raynes’ methods substituted into Gagnon would further and predictably remove the lipoprotein fraction from blood serum.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Affidavit/Declaration
The Declaration under 37 CFR 1.132 filed 4/13/2026 is insufficient to overcome the obviousness rejection of claims 44-49 based upon Gagnon and in view of Mahn as set forth in the last Office action because:
It refer(s) only to the system described in the above referenced application and not to the individual claims of the application. Thus, there is no showing that the objective evidence of nonobviousness is commensurate in scope with the claims. See MPEP § 716, and
It include(s) statements which amount to an affirmation that the claimed subject matter functions as it was intended to function. This is not relevant to the issue of nonobviousness of the claimed subject matter and provides no objective evidence thereof. See MPEP § 716.
The instant Declaration has not presented any new factual evidence of nonobviousness at this time, only cites the specific portions of the specification, and appears to ignore that Gagnon expressly contemplates hydrophobic interaction chromatography (HIC) as an alternative embodiment at [0133] and so any ability of the claimed extracellular vesicles to not bind to the HIC and subsequent collection thereof is subsumed by the HIC of Gagnon, and Mahn teaches known hydrophobic moieties for HIC. None of the inventor’s arguments persuasive show that the HIC contemplated by Gagnon is otherwise inoperable, see M.P.E.P. § 716.01(c). As such, the inventor’s conclusion that the claimed methods are nonobvious is not persuasive at this time; see M.P.E.P. § 716.01(c)(III).
In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
Response to Arguments
Applicant's arguments on pages 5-11 of the reply have been fully considered, but not found persuasive of error for the reasons given below. Any arguments over the instant Declaration are fully addressed above.
Applicant’s arguments on pages 7-9 of the reply are not persuasive, because they appear to ignore that Gagnon expressly contemplates hydrophobic interaction chromatography (HIC) as an alternative embodiment at [0133] and so any ability of the claimed extracellular vesicles to not bind to the HIC and subsequent collection thereof is subsumed by the HIC of Gagnon, and Mahn teaches known hydrophobic moieties for HIC. Applicant is reminded that a reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments; see M.P.E.P. § 2123.
As such, Applicant’s arguments on pages 10-11 of the reply that Gagnon teaches away from the claimed HIC methods is not persuasive because nothing in Gagnon criticizes, discredits, or otherwise discourage the claimed HIC methods. Furthermore, preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). Gagnon cannot reasonably be construed as teaching away from the claimed HIC methods when Gagnon expressly contemplates hydrophobic interaction chromatography (HIC) as an alternative embodiment at [0133].
On page 6 of the reply of the reply, Applicant alleges that the instant amendments to claim 44 overcomes the obviousness rejection of record over Gagnon. While this is persuasive, new grounds of rejection in view over Gagnon in view of Mahn are set forth above and the arguments are not persuasive over the combination of references. Gagnon is no longer applied alone, but in combination with Mahn and so and the claimed invention becomes obvious when the references are considered together as a whole rather than each alone.
In response to applicant's argument that the references fail to show certain features of the invention on page 7 of the reply, it is noted that the features upon which applicant relies (i.e., the extracellular vesicles do not bind to the stationary phase) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). In this case, the argument is not reasonably commensurate to the scope of the claim because claim 44 is generic on what interaction the extracellular vesicles have with the hydrophobic interaction column and Gagnon is still pertinent for the prima facie case for obviousness set forth above.
Conclusion
No claims are allowed. No claims are free of the art.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEAN C BARRON whose telephone number is (571)270-5111. The examiner can normally be reached 7:30am-3:30pm EDT/EST (M-F).
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/Sean C. Barron/Primary Examiner, Art Unit 1653
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